Semaglutide is an injectable drug for diabetes in the class called GLP-1 analogues. Click for my overview of the class. Semaglutide is sold in the U.S. as brand name Ozempic.
Folks with diabetes taking Ozempic found that it promoted fat weight loss. Facial fat tends to fill in wrinkles, hence, younger-looking skin. Loss of fat on the face can make your skin sag and older-looking, more wrinkled, gaunt. That’s so-called Ozempic face.
Semaglutide and others in it’s class are increasingly being used by non-diabetics for weight loss, either as an injection or a pill.
To restore volume in a patient’s face, doctors will often perform noninvasive, but expensive, procedures such as injecting Radiesse and hyaluronic acid-based fillers or Sculptra injections, which stimulates collagen production. Doctors can also restore volume with a face lift or by transferring fat from other body parts to the face.
I have nothing against Prilosec in particular. It can be very helpful. It’s one of several PPIs on the market.
Proton Pump Inhibitor drugs (PPIs) greatly reduce the production of acid in the stomach. They revolutionized and improved the treatment of ulcers in the stomach and duodenum. When I started medical practice in 1981, I saw many patients who had required stomach surgery to treat their ulcers. Remember the good ol’ Billroth procedures? Of course you don’t. The first PPI approved for use in the US. was cimetidine (Tagamet) in 1979.
But wait, you say. “Isn’t there a reason we have stomach acid in the first place?” Good question! Because if we reduce stomach acid, it may cause problems. Regardless of what acid contributes to food digestion, it also kills germs in food and water. Germs that may kill us if ignored. Most of us in the developed world would be horrified to drink untreated water out of a lake, stream, river, or spring. But what do you think Homo sapiens did for most our 200,000 years of our existence?
Omeprazole was made over the counter in 2003 but I don’t think these drugs should ever have been made available without prescription. PPIs are powerful drugs that treat heartburn by reducing gastric acid production. This is accomplished by PPI binding to the hydrogen/potassium ATPase enzyme on gastric parietal cells lining the stomach. PPIs do more than block acid. They are associated with an increased risk of congestive heart failure, kidney disease, long bone fractures, and dementia, vitamin B12 deficiency, reviewed here. Regular use of proton pump inhibitors is associated with increased incidence of type two diabetes, about 24% higher compared to non-users of the drug. Proton pump inhibitors are also linked an with increased risk of small intestinal bacterial overgrowth (which is a clue as to why these drugs can be harmful). They also increase the risk of infection by Clostridiales difficile by about 2x.
Most of these individual observational studies are unable to establish causation, but the preponderance of evidence points to PPIs causing harm.
Dr Alcock also found evidence that PPI users who catch COVID-19 have 1.6x increased risk for severe disease and death.
If you’re prescribed a PPI for chronic use, check with your physician to see if you still need it. Occasional use for heartburn shouldn’t be a problem. For chronic heartburn, consider a low-carb diet and stop nocturnal alcohol consumption.
From the U.S. Food and Drug Administration May 13, 2022:
Today, the U.S. Food and Drug Administration approved Mounjaro (tirzepatide) injection to improve blood sugar control in adults with type 2 diabetes, as an addition to diet and exercise. Mounjaro was effective at improving blood sugar and was more effective than the other diabetes therapies with which it was compared in clinical studies.
“Given the challenges many patients experience in achieving their target blood sugar goals, today’s approval of Mounjaro is an important advance in the treatment of type 2 diabetes,” said Patrick Archdeacon, M.D., associate director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research.
Type 2 diabetes, the most common form of diabetes, is a chronic and progressive condition in which the body does not make or use insulin normally, leading to high levels of glucose (sugar) in the blood. More than 30 million Americans have type 2 diabetes. Despite the availability of many medications to treat diabetes, many patients do not achieve the recommended blood sugar goals.
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are hormones involved in blood sugar control. Mounjaro is a first-in-class medicine that activates both the GLP-1 and GIP receptors, which leads to improved blood sugar control. Mounjaro is administered by injection under the skin once weekly, with the dose adjusted as tolerated to meet blood sugar goals.
Three different doses of Mounjaro (5 milligrams, 10 milligrams and 15 milligrams) were evaluated in five clinical trials as either a stand-alone therapy or as an add-on to other diabetes medicines. The efficacy of Mounjaro was compared to placebo, a GLP-1 receptor agonist (semaglutide) and two long-acting insulin analogs.
On average, patients randomized to receive the maximum recommended dose of Mounjaro (15 milligrams) had lowering of their hemoglobin A1c (HbA1c) level (a measure of blood sugar control) by 1.6% more than placebo when used as stand-alone therapy, and 1.5% more than placebo when used in combination with a long-acting insulin. In trials comparing Mounjaro to other diabetes medications, patients who received the maximum recommended dose of Mounjaro had lowering of their HbA1c by 0.5% more than semaglutide, 0.9% more than insulin degludec and 1.0% more than insulin glargine.
Obesity was common among study participants, with an average body mass index of 32 to 34 kilograms/height in meters squared reported at the time of enrollment. Among patients randomized to the maximum recommended dose, the average weight loss with Mounjaro was 15 pounds more than placebo when neither were used with insulin and 23 pounds more than placebo when both were used with insulin. The average weight loss with the maximum recommended dose of Mounjaro was 12 pounds more than semaglutide, 29 pounds more than insulin degludec and 27 pounds more than insulin glargine. Those patients receiving insulin without Mounjaro tended to gain weight during the study.
Mounjaro can cause nausea, vomiting, diarrhea, decreased appetite, constipation, upper abdominal discomfort and abdominal pain.
Mounjaro causes thyroid C-cell tumors in rats. It is unknown whether Mounjaro causes such tumors, including medullary thyroid cancer, in humans. Mounjaro should not be used in patients with a personal or family history of medullary thyroid cancer or in patients with Multiple Endocrine Neoplasia syndrome type 2.
Mounjaro has not been studied in patients with a history of pancreas inflammation (pancreatitis), and it is not indicated for use in patients with type 1 diabetes.
Mounjaro received priority review designation for this indication. A priority review designation directs overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions.
The starting dose is 2.5 mg subcutaneously once weekly. After four weeks dose can be increased to 5 mg once weekly. Dose can be increased every four weeks to a maximum of 15 mg once weekly.
A recent study looked at the health benefits of type 2 diabetes drugs, comparing drugs that can cause hypoglycemia and those that don’t. The very first sentence of the abstract didn’t give me much hope for what followed. That sentence was: “Different guidelines provide similar, but not identical, therapeutic targets for HbA1c in type 2 diabetes. These targets can also depend from the different pharmacological strategies adopted for intensifying glycemic control.” Did you catch the misprint?
This meta-analysis of 13 clinical trials was looking for differences in various health outcomes over the course of at least two years, comparing successful intensive management to standard care or placebo. Successful intensive management was defined as at least a 0.5% (6 mmol/mol) improvement in hemoglobin A1c (HgbA1c) level. “Intensification” of drug therapy is usually applied to a patient who is not at goal HgbA1c level. Undoubtedly, the benefits of intensification will be greater for those at HgbA1c of 10% than for those at 7.5%. BTW, few large clinical trials include patients over 75 years of age.
For my U.S. readers, note that other countries often specify HgbA1c values as mmol/mol instead of %. And blood sugars are not our usual mg/dl, but instead reported as mmol/l. HbA1c of 7% equals 53 mmol/mol, which would indicate and average blood sugar of 154 mg/dl or 8.6 mmol/l. As another example, HbA1c of 6.5% is 48 mmol/mol, reflecting average blood sugar of 140 mg/dl or 7.8 mmol/l. Are you thoroughly confused yet?
In the general population, lowest levels of mortality are seen at HgbA1c’s around 5 to 5.5% (31 to 36.6 mmol/mol). The average healthy non-diabetic adult hemoglobin A1c is 5% (31 mmol/mol) and translates into an average blood sugar of 100 mg/dl (5.56 mmol/l). This will vary a bit from lab to lab. Most healthy non-diabetics would be under 5.7% (38.8 mmol/mol). In December, 2009, the American Diabetes Association established a hemoglobin A1c criterion for the diagnosis of diabetes: 6.5% (47.5 mmol/mol) or higher. Diagnosis of prediabetes involves hemoglobin A1c in the range of 5.7 to 6.4% (38.8 to 46.5 mmol/mol).
Some expert panels recommend aiming for HgbA1c under 7% (53 mmol/mol), others recommend under 6.5% (48 mmol/mol). A major point of debate between the two guideline goals, is that the lower you set the goal, the greater the risk of drug-induced hypoglycemia, which can be lethal. In the early 1980s, the only drugs we had for diabetes were insulin, sulfonylureas, and metformin. Two of those three can can cause hypoglycemia. Now, a majority of our type 2 diabetes drugs don’t cause hypoglycemia.
If you’re at risk for hypoglycemia, teach those you hang with how to recognize and treat it
The Italian researchers did this meta-analysis as part of their effort to produce diabetes drug treatment guidelines for the Italian population. On to the study at hand…
What Did the Researchers Find?
Improved glycemic (blood sugar) control by intensive attention reduced the major cardiovascular event rate by 10% and reduced renal adverse events by 25% but did not affect overall mortality or eye complications.
Intensified therapy with hypoglycemia-inducing drugs did not reduce overall mortality.
Drugs without potential for causing hypoglycemia were linked to lower risk of major cardiovascular events, kidney adverse events, and overall mortality, for HgbA1c under 7% (53 mmol/mol).
In conclusion, the results of this meta-analysis of RCTs show that in people with T2DM the improvement of glycemic control with drugs not inducing hypoglycemia is associated with a reduction in the risk of long-term chronic vascular complications (major adverse cardiac events and renal adverse events) and all-cause mortality, at least for HbA1c levels above 7%. The reduction of HbA1c below that threshold could have some favorable effects, but there is no available direct evidence in this respect. When the reduction of HbA1c is achieved with drugs inducing hypoglycemia, a progressive reduction of complications and an increase in the risk of severe hypoglycemia is observed. Therefore, the choice of the most adequate HbA1c target for each patient with T2DM should be made considering an appropriate risk/benefit ratio.
I think the researchers were particularly glad to find that intensification of drug therapy can reduce risk of heart attack, stroke, kidney complications, and death; all this without the risk of hypoglycemia that comes with drugs like insulin and sulfonylureas. The lack of a mortality benefit from hypoglycemia-inducing drugs may also be important. The benefits of intensive drug therapy (or lack thereof) depend somewhat on the particular complication you’re trying to avoid, and on baseline HgbA1c. Drug therapy is complicated! I expect these researchers would recommend a treatment HgbA1c goal of <7% rather than <6.5%.
Steve Parker, M.D.
PS: Reduce your need for diabetes drugs by losing excess weight, exercising, and eating low-carb.
FDA has approved Kerendia (finerenone) tablets to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes.
Diabetes is the leading cause of chronic kidney disease and kidney failure in the United States. Chronic kidney disease occurs when the kidneys are damaged and cannot filter blood normally. Because of defective filtering, patients can have complications related to fluid, electrolytes (minerals required for many bodily processes), and waste build-up in the body. Chronic kidney disease sometimes can progress to kidney failure. Patients also are at high risk of heart disease.
The efficacy of Kerendia to improve kidney and heart outcomes was evaluated in a randomized, multicenter, double-blind, placebo-controlled study in adults with chronic kidney disease associated with type 2 diabetes. In this study, 5,674 patients were randomly assigned to receive either Kerendia or a placebo.
The study compared the two groups for the number of patients whose disease progressed to a composite (or combined) endpoint that included at least a 40% reduction in kidney function, progression to kidney failure, or kidney death. Results showed that 504 of the 2,833 patients who received Kerendia had at least one of the events in the composite endpoint compared to 600 of the 2,841 patients who received a placebo.
The study also compared the two groups for the number of patients who experienced cardiovascular death, a non-fatal heart attack, non-fatal stroke, or hospitalization for heart failure. Results showed that 367 of the 2,833 patients receiving Kerendia had at least one of the events in the composite endpoint compared to 420 of the 2,841 patients who received a placebo, with the treatment showing a reduction in the risk of cardiovascular death, non-fatal heart attack, and hospitalization for heart failure.
Side effects of Kerendia include hyperkalemia (high levels of potassium), hypotension (low blood pressure), and hyponatremia (low levels of sodium). Patients with adrenal insufficiency (when the body does not produce enough of certain hormones) and those receiving simultaneous treatment with strong CYP3A4 inhibitors should not take Kerendia.
Kerendia received priority review and fast track designations for this application.
FDA granted the approval of Kerendia to Bayer Healthcare.
Just offhand, finerenone doesn’t look like a great drug. Helpful, maybe. Chronic kidney disease can end up at ESRD (end stage renal disease), which requires thrice weekly hemodialysis if the patient wants to stay alive. (Yes, peritoneal dialysis is an alternative.) Preventing ESRD is an incredible benefit for an individual.
Finerenone seems to be a well-tolerated daily pill. The main adverse effect is elevated blood potassium level, which can cause palpitations, and death infrequently. Less commonly, the drug can cause low blood pressure.
The ultimate role of finerenone in our armamentarium against disease and suffering will probably depend on cost and the number needed to treat.
This Shrimp Salad is low-carb. Use the search box for recipe.
Christine Fallabel has an article at Diabetes Daily that may save you beaucoup bucks on your diabetes care, whether or not you have insurance coverage.
If you live in a country like the United States, where the majority of health insurance is privatized and there is no strong social safety net, it can feel as though managing a chronic disease like diabetes requires nothing but lots of money. And it does. As of 2017, diabetes cost the United States a staggering $327 billion dollars per year on direct health care costs, and people with diabetes average 2.3x higher health care costs per year than people living without the disease.
Diabetes is also devastatingly expensive personally: the cost of insulin has risen over 1200% in the past few decades, with no change to the chemical formula. In 1996, when Eli Lilly’s Humalog was first released, the price for a vial of insulin was $21. In 2019, that same vial costs around $275. Studies show that 1 in 4 people ration insulin simply due to cost. Diabetes Daily recently conducted a survey study, with almost 2,000 participants, of which an overwhelming 44% reported struggling to afford their insulin.
So where does this leave patients who don’t have tons of money to spend on insulin and supplies, or who don’t have adequate health insurance coverage for the technology to help prevent complications? Can you manage diabetes well without lots of money? The short answer is yes. The long answer is a bit more complicated.
Medical Xpress has an article about the possible future uses of metformin for weight loss, prostate cancer treatment, and tuberculosis treatment. It didn’t mention metformin as an anti-aging drug.
From the article:
Among medications, metformin has a long and storied past. The compound destined to become metformin was first isolated during the Middle Ages from the French lilac, a plant scientifically known as Galega officinalis. Ground flowers and leaves were administered by healers to patients suffering from constant urination, a hallmark of a disorder that later would become known as diabetes. The active ingredient in French lilac, a plant also called goat’s rue, was identified hundreds of years later as galegine, which triggered a striking reduction in blood glucose.
By the 1950s, scientists were able to exploit folk medicine uses and develop the drug that became metformin.
Don’t believe everything you read. The article claims metformin’s effectiveness in type 2 diabetes is primarily due to weight loss. Conventional thinking is that it’s mostly due to decreased production and release of glucose by the liver. I guess time will tell which theory wins out. In either case, it’s a good initial drug for T2 diabetes if diet and exercise prove inadequate.
Steve Parker, M.D.
Click pic to purchase book at Amazon.com. E-book versions available at Smashwords.com.
Everyone with diabetes—whether type 1 or type 2—should know that the amount of carbohydrate in meals has an impact on blood sugar levels and insulin requirements. In general, the more carbs, the more insulin you need, whether that insulin comes from a pharmacy or your pancreas. Less well known is that dietary protein and fat also have an effect on insulin requirements. It’s complicated, and there’s quite a bit of variation from one individual to another. The study at hand involved folks with type 1 diabetes using an insulin pump. The test meal was a piece of bread (pane di casa, 45 g carb) plus avocado and other fats in varying amounts.
From Diabetes Care:
The current study has two important outcomes. First, the type of fat has no statistically or clinically significant impact on postprandial glycemia, but the amount of fat has a significant, dose-dependent effect. Second, the insulin delivery pattern, and in some cases total dose, needs to be adjusted based on the amount of fat in order to minimize the risk of early postprandial hypoglycemia and late postprandial hyperglycemia.
Paleo Diabetic 